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Background: Haemoglobin drop is common in acute coronary syndrome (ACS) patients and correlates with poor prognosis. However, the association between mild haemoglobin drop and adverse clinical outcome remains insufficiently investigated. This study aimed to examine the association between in-hospital haemoglobin drop and risk for adverse clinical outcomes in ACS patients, especially those with mild drop., Methods: Included patients from the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged after an Acute Coronary Syndrome) registry were categorized into three groups by the presence and amount of in-hospital haemoglobin drop (non-drop, mild drop and severe drop). The cut-off point between mild drop and severe drop is ≥ 3 g/dL. Multivariate Cox regression was used to assess the association between haemoglobin drop and major adverse cardiac endpoints (MACE). Patients taking potent P2Y 12 inhibitors were selected for the additional analysis. Propensity score matching was used to avoid selective bias in the additional analysis., Results: Of 6911 patients, 4949 patients (71.6%) experienced in-hospital haemoglobin drop. Compare with non-drop group, patients with haemoglobin drop had higher risk of MACE [adjusted hazard ratio (HR) = 1.36, 95% CI: 1.03-1.80 for mild drop group; adjusted HR = 1.70, 95% CI: 1.07-2.68 for severe drop group]. Patients in mild drop group were less likely to receive potent P2Y 12 inhibitors at discharge (mild drop group vs. severe drop group vs. non-drop group: 10.9% vs. 10.7% vs. 23.8%). After propensity score matching adjustment among patients with potent P2Y 12 inhibitors, patients in mild drop group were not associated with an increased risk of MACE than those in non-drop group (adjusted HR = 1.52, 95% CI: 0.49-4.72)., Conclusions: In-hospital haemoglobin drop was common in ACS patients and associated with a higher risk for adverse events. Reduced prescription for potent P2Y 12 inhibitors may be responsible for poor prognoses among patients with mild haemoglobin drop., (© 2022 JGC All rights reserved; www.jgc301.com.)

Background: Transcatheter aortic valve implantation (TAVI) is an established management strategy for severe aortic valve stenosis. Percutaneous axillary approach for TAVI holds the promise of improving safety without jeopardizing effectiveness in comparison to surgical access. We aimed at appraising the comparative effectiveness of percutaneous vs. surgical axillary approaches for TAVI., Methods: We performed an international retrospective observational study using de-identified details on baseline, procedural, and 1-month follow-up features. Valve Academic Research Consortium (VARC)-3 criteria were applied throughout. Outcomes of interest were clinical events up to 1 month of follow-up, compared with unadjusted and propensity score-adjusted analyses., Results: A total of 432 patients were included, 189 (43.8%) receiving surgical access, and 243 (56.2%) undergoing percutaneous access. Primary hemostasis failure was more common in the percutaneous group (13.2% vs. 4.2%, P<0.001), leading to more common use of covered stent implantation (13.2% vs. 3.7%, P<0.001). Irrespectively, percutaneous access was associated with shorter hospital stay (-2.6 days [95% confidence interval: -5.0; -0.1], P=0.038), a lower risk of major adverse events (a composite of death, myocardial infarction, stroke, type 3 bleeding, and major access-site related complication; odds ratio=0.44 [0.21; 0.95], P=0.036), major access-site non-vascular complications (odds ratio=0.21 [0.06; 0.77], P=0.018), and brachial plexus impairment (odds ratio=0.16 [0.03; 0.76], P=0.021), and shorter hospital stay (-2.6 days [-5.0; -0.1], P=0.038)., Conclusions: Percutaneous axillary access provides similar or better results than surgical access in patients undergoing TAVI with absolute or relative contraindications to femoral access.

Aims: To assess the impact of secondary prevention medical therapies (statins, ACE-inhibitors/Angiotensin Receptor Blockers (ARB), beta-blockers (BB) and Dual Antiplatelet Therapy (DAPT)) on outcomes of patients with myocardial infarction with nonobstructive coronary artery disease (MINOCA)., Methods: Five adjusted observational studies encompassing 10,546 were included in this meta-analysis. All-cause death was the primary endpoint, while Major Adverse Cardiovascular Events (MACE) and acute myocardial infarction (AMI) were the secondary endpoints., Results: After 24 months of follow up, statins (tested in 8093 patients) were associated with a reduced risk of all-cause death (HR 0.60:0.45-0.81, p 〈0,001), while ACE-inhibitors/ARB (on 9666 patients) were not. Aggregate data from two studies (n = 9720, 7719 on beta-blockers, 6423 on DAPT) indicated that beta-blockers and DAPT (median follow-up 34.1 and 15.7 months, respectively) were both associated with a significant reduction of all-cause death (HR0.81:0.66-0.99, p = 0.04, and HR0.73:0.55-0.98, p = 0.03, for beta-blockers and DAPT, respectively). Among the investigated therapies, only ACE-inhibitors/ARBs entailed a reduced risk of MACE (HR0.65:0.44-0.94, p = 0.02, all CI 95%) over 36.5 months (four studies, n = 10,150). None of the investigated therapies was associated with a reduced risk of AMI., Conclusions: Data from adjusted observational studies suggest that beta-blockers, statins and DAPT are associated with a survival benefit among MINOCA patients. ACE-inhibitors/ARB entail a reduced risk of MACE while none of the investigated secondary prevention therapies is associated with a reduced risk of AMI. Randomized controlled trials are warranted to confirm these findings., Competing Interests: Declaration of Competing Interest None, (Copyright © 2022 Elsevier B.V. All rights reserved.)

Aims: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]., Methods and Results: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk., Conclusion: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Hemodynamics interacts with the cellular components of human vessels, influencing function and healthy status. Locally acting hemodynamic forces have been associated-by a steadily increasing amount of scientific evidence-with nucleation and evolution of atherosclerotic plaques in several vascular regions, resulting in the formulation of the 'hemodynamic risk hypothesis' of the atherogenesis. At the level of coronary arteries, however, the complexity of both anatomy and physiology made the study of this vascular region particularly difficult for researchers. Developments in computational fluid dynamics (CFD) have recently allowed an accurate modelling of the intracoronary hemodynamics, thus offering physicians a unique tool for the investigation of this crucial human system by means of advanced mathematical simulations. The present review of CFD applications in coronary artery disease was set to concisely offer the medical reader the theoretical foundations of quantitative intravascular hemodynamics-reasoned schematically in the text in its basic (i.e., pressure and velocity) and derived quantities (e.g., fractional flow reserve, wall shear stress and helicity)-along with its current implications in clinical research. Moreover, attention was paid in classifying computational modelling derived from invasive and non-invasive imaging modalities with unbiased remarks on the advantages and limitations of each procedure. Finally, an extensive description-aided by explanatory figures and cross references to recent clinical findings-was presented on the role of near-wall hemodynamics, in terms of shear stress, and of intravascular flow complexity, in terms of helical flow., Competing Interests: The author declares no conflict of interest. Fabrizio D’Ascenzo is serving as one of the Editorial Board members of this journal. We declare that Fabrizio D’Ascenzo had no involvement in the peer review of this article and has no access to information regarding its peer review. Full responsibility for the editorial process for this article was delegated to Jerome L. Fleg., (Copyright: © 2022 The Author(s). Published by IMR Press.)

Current guidelines support the use of transcatheter edge-to-edge repair (TEER) for patients with both primary and secondary mitral regurgitation. We aimed to compare the prognoses of TEER in degenerative mitral regurgitation (DMR) vs. functional mitral regurgitation (FMR). A total of 208 consecutive patients who underwent TEER over a ten-year period were analyzed. Primary endpoints included rates of all-cause death and major adverse cardiac events (MACE: composite of all-cause death, hospitalizations for heart failure, mitral valve surgery, or TEER re-intervention). A total of 148 (71%) patients were identified with FMR, while 60 (29%) were identified with DMR. Patients in the FMR group were younger (77.2 ± 8.4 vs. 80.2 ± 7.2, p = 0.02), suffered more frequently from coronary artery disease (54.1% vs. 10.0%, p = 0.02), and atrial fibrillation/flutter (70.9% vs. 38.3%, p = 0.02). Rates of 1-year death (21.6% vs. 10.0%, p = 0.03) and MACE (41.2% vs. 21.7%, p = 0.02) were higher for the FMR group, as compared to the DMR group. After correcting for variables, FMR independently predicted rates of MACE (HR-1.78, 95% CI 1.23-2.48, p = 0.04) and had a non-significant effect on one-year mortality (HR-1.67, 95%CI 0.98-3.74, p = 0.07). In our experience, worse overall 1-year composite MACE outcomes were observed after TEER in patients with FMR as compared to patients with DMR.

Background Acute kidney injury (AKI) after transcatheter aortic valve replacement (TAVR) is associated with increased mortality. However, it is controversial whether AKI affects prognosis per se, being linked to baseline chronic kidney disease (CKD) and bleeding complications. The aim of this study was to disentangle, applying mediation analysis, the association between AKI and clinical outcome, considering CKD and bleedings. Methods and Results Consecutive patients undergoing TAVR were prospectively enrolled at 5 high-volume centers in Italy. AKI was defined according to Valve Academic Research Consortium-3 consensus, whereas bleeding with Bleeding Academic Research Consortium. Primary outcome was all-cause mortality after 1-year follow-up. Among 2621 patients undergoing TAVR, AKI occurrence was associated with 1-year mortality. This association of AKI with the primary end points remained significant after adjusting for baseline risk estimators, either Society of Thoracic Surgeons score (hazard ratio [HR], 2.78 [95% CI, 1.95-3.80], P <0.001) or EuroSCORE-II (HR, 1.85 [95% CI, 1.35-2.56], P <0.001). Both AKI and CKD significantly and independently affected primary outcome (HR, 3.06 [95% CI, 2.01-4.64], P <0.001 and HR, 1.82 [95% CI 1.27-2.65], P <0.01, respectively). The estimated proportion of the total effect of CKD mediated via AKI was, on average, 15%, 95% CI, 4%-29%, P <0.001. The significant effect of Bleeding Academic Research Consortium 2-5 bleedings on the primary outcome was not mediated by AKI. Conclusions AKI occurs in 1 out of 6 patients and significantly mediates one fifth of the effect of baseline CKD on all-cause mortality after TAVR. Our analysis supports a systematic effort to prevent AKI during TAVR, which may potentially translate into improved patients' 1-year survival.

Background: Coronary chronic total occlusion lesions (CTOs) confer an increased risk of arrhythmic events among patients with ischemic cardiomyopathy (ICM) and implantable cardioverter-defibrillator (ICD) carriers, however the impact of CTO recanalization in this population remains unassessed., Aims: Evaluate the impact of CTOs percutaneous coronary interventions (PCI) on arrhythmic events., Methods: Patients with ICM and ICD from the VACTO I-II registries: patients with medically treated CTO (CTO-OMT group) and without CTO (no-CTO group) were compared after inverse-probability-weighting adjustment (IPWT) with a similar population of consecutive patients undergoing CTO-PCI. The primary endpoint was appropriate ICD therapy. The secondary endpoint was all-cause mortality., Results: The total of 622 patients (mean age 67 ± 10 years, mean left ventricular ejection fraction 36 ± 11%) included in the analysis was composed by: CTO-PCI patients n = 113, CTO-OMT patients n = 286, no-CTO patients n = 223. In the CTO-PCI group, compared to the CTO-OMT group, 5-year Kaplan Meier estimates for appropriate ICD therapy (20.4% vs. 56.4%, IPW-adjusted HR: 0.45, 95% CI 0.29-0.71) and mortality (8.8% vs. 23%, IPW-adjusted HR: 0.43, 95% CI 0.22-0.85) were lower, driven by infarct related artery CTO (IRA-CTO) PCI, while similar to those occurring in the no-CTO group., Conclusions: In this large population, those with CTO receiving PCI had lower arrhythmic event rates and lower mortality compared to the CTO-OMT group, while showing an event rate similar to no-CTO patients. Sensitivity analyses suggest that the beneficial effect on the arrhythmic outcome was driven by IRA-CTO revascularization., Classification: Chronic total occlusion., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Postoperative acute kidney injury (AKI) is frequent in cardiac surgery patients. Its pathophysiology is complex and involves decreased renal perfusion. Preliminary clinical evidence in critically ill patients shows that amino acids infusion increases renal blood flow and may decrease the incidence and severity of AKI. We designed a study to evaluate the effectiveness of perioperative continuous infusion of amino acids in decreasing AKI., Methods: This is a phase III, multi-center, randomized, double-blind, placebo-controlled trial. Adults undergoing cardiac surgery with cardiopulmonary bypass (CPB) are included. Patients are randomly assigned to receive either continuous infusion of a balanced mixture of amino acids in a dose of 2 g/kg ideal body weight/day or placebo (balanced crystalloid solution) from the operating room up to start of renal replacement therapy (RRT), or ICU discharge, or 72 h after the first dose. The primary outcome is the incidence of AKI during hospital stay defined by KDIGO (Kidney Disease: Improving Global Outcomes). Secondary outcomes include the need for, and duration of, RRT, mechanical ventilation; ICU and hospital length of stay; all-cause mortality at ICU, hospital discharge, 30, 90, and 180 days after randomization; quality of life at 180 days. Data will be analyzed in 3500 patients on an intention-to-treat basis., Discussion: The trial is ongoing and currently recruiting. It will be one of the first randomized controlled studies to assess the relationship between amino acids use and kidney injury in cardiac surgery. If our hypothesis is confirmed, this practice could reduce morbidity in the studied population., Study Registration: This trial was registered on ClinicalTrials.gov with the trial identification NCT03709264 in October 2018., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Bifurcation percutaneous coronary intervention (PCI) is associated with higher risk of clinical events., Objectives: This study aimed to determine clinical and lesion features that predict adverse outcomes, and to evaluate the differential prognostic impact of these features in patients undergoing PCI for bifurcation lesions., Methods: We analyzed 5,537 patients from the BIFURCAT (comBined Insights From the Unified RAIN and COBIS bifurcAtion regisTries) registry. The primary outcome was major adverse cardiac events (MACE) at 2-year follow-up; secondary outcomes included hard endpoints (all-cause death, myocardial infarction) and lesion-oriented clinical outcomes (LOCO) (target-vessel myocardial infarction, target lesion revascularization). The least absolute shrinkage and selection operator (LASSO) model was used for feature selection., Results: During the 2-year follow-up period, MACE occurred in 492 patients (8.9%). The LASSO model identified 5 clinical features (old age, chronic renal disease, diabetes mellitus, current smoking, and left ventricular dysfunction) and 4 lesion features (left main disease, proximal main branch disease, side branch disease, and a small main branch diameter) as significant features that predict MACE. A combination of all 9 features improved the predictive value for MACE compared with clinical and lesion features (area under the receiver-operating characteristics curve: 0.657 vs 0.636 vs 0.581; P  < 0.001). For secondary endpoints, the clinical features had a higher impact than lesion features on hard endpoints, whereas lesion features had a higher impact than clinical features on LOCO., Conclusions: In bifurcation PCI, 9 features were associated with MACE. Clinical features were predominant predictors for hard endpoints, and lesion features were predominant for predicting LOCO. Clinical and lesion features have distinct values, and both should be considered in bifurcation PCI., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Aims: As the indications to transcatheter aortic valve replacement (TAVR) expand to patients at increasingly lower risk, procedure-related vascular and bleeding complications events must be minimized. We aimed to evaluate the impact of different large-bore arterial access closure devices on clinical outcomes after TAVR., Methods and Results: We searched for papers that reported outcomes according to the type of vascular closure device/technique used after TAVR and performed a Bayesian network meta-analysis (NMA). Fifteen studies involving 9259 patients who underwent access site closure using PROSTAR™ XL percutaneous vascular surgical system (Abbott Vascular, Santa Clara, CA, USA), Perclose ProGlide™ suture-mediated closure system (Abbott), or MANTA TM vascular closure device (Teleflex, Morrisville, NC, USA) were included. NMA showed MANTA to have the highest likelihood of reducing a primary composite endpoint of intra-hospital death, major vascular complications, and major or life-threatening bleedings [surface under the cumulative ranking curve analysis (SUCRA) 94.8%], but this was mitigated when only randomized clinical trials and propensity-matched cohorts were included (SUCRA 56.1%). The ProGlide showed the highest likelihood to reduce major or life-threatening bleedings, especially with increasing procedural complexity, and the MANTA device to reduce major and minor vascular complications. The ProStar XL device performed poorly in all explored endpoints., Conclusion: Available evidence summarized through a NMA shows that ProGlide and MANTA devices appear to be both valid vascular closure devices globally and to be the best options to minimize vascular complications and reduce bleeding in patients undergoing TAVR, respectively., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objectives: The aim of this study was to evaluate outcomes of real-world patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) with the 34 mm Evolut R (Medtronic, Minneapolis, Minnesota)., Background: Larger aortic annulus has been associated with increased incidence of paravalvular leaks (PVLs) after TAVR. However, little is known, so far, about the performance of the 34 mm Evolut R in this setting., Methods: From the multicenter, international, retrospective Horizontal Aorta in Transcatheter Self-expanding Valves (HORSE) registry, including patients who underwent TAVR for native severe AS, we selected patients treated with the 34 mm Evolut R evaluating procedural characteristics and VARC-2 defined device success. We also compared 34 mm Evolut R with other Evolut R sizes., Results: Among the 4434 patients included in the registry, 572 (13%) received the 34 mm Evolut R valve. Mean age was 80.8 ± 6.5 years and the median STS PROM score was 4 [interquartile range 2-6]. Device success was achieved in 87.4% with 7.7% of PVLs; moreover, the rate of permanent pacemaker implantation (PPMI) was 22.4%. Patients who underwent 34 mm Evolut R implantation experienced more in-hospital permanent pacemaker implantation (22.4% vs. 15%; p < 0.001). At multivariate analysis, 34 mm Evolut R did not affect device success (OR: 0.81 [0.60-1.09]; p = 0.151). Device success was consistent with other THVs sizes (87.4% vs. 89.6%; p = 0.157)., Conclusions: THV replacement in patients requiring 34 mm Evolut R has an acceptable performance. Compared to other Medtronic sizes it demonstrated to be comparable in terms of device success, despite an increased rate of pacemaker implantation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Tumour molecular annotation is mandatory for biomarker discovery and personalised approaches, particularly in triple-negative breast cancer (TNBC) lacking effective treatment options. In this study, the interleukin-3 receptor α (IL-3Rα) was investigated as a prognostic biomarker and therapeutic target in TNBC. IL-3Rα expression and patients' clinical and pathological features were retrospectively analysed in 421 TNBC patients. IL-3Rα was expressed in 69% human TNBC samples, and its expression was associated with nodal metastases ( p = 0.026) and poor overall survival (hazard ratio = 1.50; 95% CI = 1.01-2.2; p = 0.04). The bioinformatics analysis on the Breast Invasive Carcinoma dataset of The Cancer Genome Atlas (TCGA) proved that IL-3Rα was highly expressed in TNBC compared with luminal breast cancers ( p = 0.017, p adj = 0.026). Functional studies demonstrated that IL-3Rα activation induced epithelial-to-endothelial and epithelial-to-mesenchymal transition, promoted large blood lacunae and lung metastasis formation, and increased programmed-cell death ligand-1 (PD-L1) in primary tumours and metastases. Based on the TCGA data, IL-3Rα, PD-L1, and EMT coding genes were proposed to discriminate against TNBC aggressiveness (AUC = 0.86 95% CI = 0.82-0.89). Overall, this study identified IL-3Rα as an additional novel biomarker of TNBC aggressiveness and provided the rationale to further investigate its relevance as a therapeutic target.

Objective: To evaluate the diagnostic accuracy of coronary computed tomography angiography (CCTA) for the evaluation of obstructive coronary artery disease (CAD) in patients referred for transcatheter aortic valve implantation (TAVI)., Methods: EMBASE, PubMed/MEDLINE, and CENTRAL were searched for studies reporting accuracy of CCTA for the evaluation of obstructive CAD compared with invasive coronary angiography (ICA) as the reference standard. QUADAS-2 tool was used to assess the risk of bias. A bivariate random effects model was used to analyze, pool, and plot the diagnostic performance measurements across studies. Pooled sensitivity, specificity, positive ( + LR) and negative (-LR) likelihood ratio, diagnostic odds ratio (DOR), and hierarchical summary ROC curve (HSROC) were evaluated. Prospero registration number: CRD42021252527., Results: Fourteen studies (2533 patients) were included. In the intention-to-diagnose patient-level analysis, sensitivity and specificity for CCTA were 97% (95% CI: 94-98%) and 68% (95% CI: 56-68%), respectively, and + LR and -LR were 3.0 (95% CI: 2.1-4.3) and 0.05 (95% CI: 0.03 - 0.09), with DOR equal to 60 (95% CI: 30-121). The area under the HSROC curve was 0.96 (95% CI: 0.94-0.98). No significant difference in sensitivity was found between single-heartbeat and other CT scanners (96% (95% CI: 90 - 99%) vs. 97% (95% CI: 94-98%) respectively; p = 0.37), whereas the specificity of single-heartbeat scanners was higher (82% (95% CI: 66-92%) vs. 60% (95% CI: 46 - 72%) respectively; p < 0.0001). Routine CCTA in the pre-TAVI workup could save 41% (95% CI: 34 - 47%) of ICAs if a disease prevalence of 40% is assumed., Conclusions: CCTA proved an excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI; the use of single-heartbeat CT scanners can further improve these findings., Key Points: • CCTA proved to have an excellent diagnostic accuracy for assessing obstructive CAD in patients referred for TAVI. • Routine CCTA in the pre-TAVI workup could save more than 40% of ICAs. • Single-heartbeat CT scanners had higher specificity than others in the assessment of obstructive CAD in patients referred for TAVI., (© 2022. The Author(s).)

Background: Cardiac involvement significantly contributes to coronavirus disease 2019 (COVID-19) mortality.12-lead electrocardiogram (ECG) represents a fast, cheap, and easy to perform exam with the adjunctive advantage of the remote reporting possibility. In this study, we sought to investigate if electrocardiographic parameters can identify patients, deemed at low-risk at admission, who will face in-hospital unfavorable course., Methods: From March 1, 2020, through March 30, 2021, 384 consecutive patients with confirmed low-risk COVID-19 were hospitalized at the University Hospital of Bari (Italy). Criteria for low risk were: admission to the division of Pneumology or Infectious Diseases, no need for immediate (within 24 hours from admission) transfer to Intensive Care Unit or for respiratory support with invasive mechanical ventilation (IMV) or for circulation support (either mechanical or pharmacological). Admission ECGs were reviewed and interpreted by two expert cardiologists. The primary outcomes were in-hospital death and the composite outcome of in-hospital death and IMV., Results: In low-risk COVID-19 patients, atrial fibrillation (AF), poor R wave progression (PRWP), tachycardia, and right bundle branch block (RBBB) resulted as statistically significant and independent predictors of in-hospital all-cause mortality; AF, PRWP, Tachycardia, RBBB, and corrected QT interval showed to be statistically significant and independent risk factors for the occurrence of the composite endpoint of death and IMV., Conclusions: Our study demonstrated for the first time that RBBB and PRWP, assessed upon admission with ECG, are associated with unfavorable clinical course in a baseline low-risk population hospitalized for COVID-19.

Acute pulmonary embolism (PE) is a common disease associated with high mortality rates that vary widely according to patient clinical presentation and hemodynamic status. According to international guidelines, systemic thrombolysis (ST) is the mainstem treatment in patients with high risk PE and intermediate-high risk PE evolving towards hemodynamic decompensation, showing lower mortality compared with anticoagulant therapy alone despite a high rate of bleeding events. Considering that a large proportion of patients presents contraindication to ST, catheter-directed therapies (CDTs) could tackle some unsolved issues, targeting the treatment to the pulmonary arteries, avoiding the dreaded complications of ST.The aim of this review is to describe the current indication for CDTs in terms of patient selection and timing of treatment, to describe contemporary available medical devices and techniques, discussing current knowledge of safety and efficacy and the importance of multidisciplinary team in PE management.

Introduction: Despite limited to short and midterm outcomes, valve-in-valve (ViV) transcatheter aortic valve implantation (TAVI) has emerged as a valid alternative to re-surgical aortic valve replacement (re-SAVR) for high- and intermediate-risk patients with degenerated surgical bioprosthesis., Methods: All studies comparing multivariate adjustment between ViV TAVI and re-SAVR were screened. The primary end-points were all-cause and cardiovascular (CV) mortality at 30 days and at Midterm follow-up. Short-term complications were the secondary endpoints., Results: We obtained data from 11 studies, encompassing 8570 patients, 4224 undergoing ViV TAVI, and 4346 re-SAVR. Four studies included intermediate-risk patients and seven high-risk patients. 30-day all-cause and CV mortality were significantly lower in ViV (odds ratio [OR] 0.43, 95% confidence intervals [CIs] 0.29-0.64 and OR 0.44, 0.26-0.73 respectively), while after a mean follow-up of 717 (180-1825) days, there was no difference between the two groups (OR 1.04, 0.87-1.25 and OR 1.05, 0.78-1.43, respectively). The risk of stroke (OR 1.03, 0.59-1.82), MI (OR 0.70, 0.34-1.44), major vascular complications (OR 0.92, 0.50-1.67), and permanent pacemaker implantation (OR 0.67, 0.36-1.25) at 30 days did not differ, while major bleedings and new-onset atrial fibrillation were significantly lower in ViV patients (OR 0.41, 0.25-0.67 and OR 0.23, 0.12-0.42, respectively, all 95% CIs)., Conclusions: In high- and intermediate-risk patients with degenerated surgical bioprostheses, ViV TAVI is associated with reduced short-term mortality, compared with re-SAVR. Nevertheless, no differences were found in all-cause and CV mortality at midterm follow-up. PROSPERO CRD42021226488., (© 2022 Wiley Periodicals LLC.)

Introduction: The impact of Impella and ECMO (ECPELLA) in cardiogenic shock (CS) remains to be defined. The aim of this meta-analysis is to evaluate the benefit of ECPELLA compared to VA-ECMO in patients with non post-pericardiotomy CS., Methods: All studies reporting short term outcomes of ECpella or VA ECMO in non post-pericardiotomy CS were included. The primary endpoint was 30-day mortality. Vascular and bleeding complications and LVAD implantation/heart transplant within 30-days were assessed as secondary outcomes., Results: Of 407 studies identified, 13 observational studies (13,682 patients, 13,270 with ECMO and 412 with ECpella) were included in this analysis. 30-day mortality was 55.8% (51.6-59.9) in the VA-ECMO group and 58.3% (53.5-63.0) in the ECpella group. At meta-regression analysis the implantation of IABP did not affect mortality in the ECMO group. The rate of major bleeding in patients on VA-ECMO and ECpella support were 21.3% (16.9-26.5) and 33.1% (25.9-41.2) respectively, while the rates of the composite outcome of LVAD implantation and heart transplantation within 30-days in patients on VA-ECMO and ECpella support were 14.4% (9.0-22.2) and 10.8%. When directly compared in 3 studies, ECpella showed a positive effect on 30-day mortality compared to ECMO (OR: 1.81: 1.039-3.159)., Conclusion: Our data suggest that ECpella may reduce 30-day mortality and increase left ventricle recovery, despite increased of bleeding rates., Competing Interests: Declaration of competing interest The authors report no relationships that could be construed as a conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Stratifying prognosis following coronary bifurcation percutaneous coronary intervention (PCI) is an unmet clinical need that may be fulfilled through the adoption of machine learning (ML) algorithms to refine outcome predictions. We sought to develop an ML-based risk stratification model built on clinical, anatomical, and procedural features to predict all-cause mortality following contemporary bifurcation PCI. Multiple ML models to predict all-cause mortality were tested on a cohort of 2393 patients (training, n = 1795; internal validation, n = 598) undergoing bifurcation PCI with contemporary stents from the real-world RAIN registry. Twenty-five commonly available patient-/lesion-related features were selected to train ML models. The best model was validated in an external cohort of 1701 patients undergoing bifurcation PCI from the DUTCH PEERS and BIO-RESORT trial cohorts. At ROC curves, the AUC for the prediction of 2-year mortality was 0.79 (0.74-0.83) in the overall population, 0.74 (0.62-0.85) at internal validation and 0.71 (0.62-0.79) at external validation. Performance at risk ranking analysis, k-center cross-validation, and continual learning confirmed the generalizability of the models, also available as an online interface. The RAIN-ML prediction model represents the first tool combining clinical, anatomical, and procedural features to predict all-cause mortality among patients undergoing contemporary bifurcation PCI with reliable performance.

Aims: Data about long-term clinical outcomes of young patients experiencing an acute myocardial infarction (MI) and about the potential impact of gender on juvenile MI incidence and prognosis are scant., Methods and Results: Hospital Discharge Register records of Piedmont region (Italy) from 2007 to 2018 were interrogated to identify incident juvenile MI cases and MI recurrences. Patients were considered young if the first MI occurred before or at 47 years of age (5th percentile). Incidence of first juvenile MI event and overall survival were the primary outcomes. Gender differences and survival rate after an MI recurrence were secondary outcomes. Out of 114.816 hospitalizations due to MI, 4482 (3.9%) occurred in people aged ≤47. Average incidence rate of juvenile MI over the study period was 24.5 (23.8-25.2) per 100.000 person-years, with a decline among men and a stable trend among women through the years. The risk of in hospital death was higher for women (1.9% vs. 0.9%, p = 0.02), while the survival rate at 10 years after the first MI was 94.8%, without gender differences (HR 1.05: 0.69-1.60). MI recurrence occurred in 348 (7.8%) and was less common in women (HR 0.72: 0.52-0.99). After multivariate adjustment, MI recurrence was associated with a significantly higher risk of death at follow-up as compared with a single MI episode (HR 3.05: 1.9-4.80, all CI 95%)., Conclusion: Among young patients with MI, women had a higher in-hospital mortality compared to men, but long-term prognosis after hospital discharge did not differ. MI recurrences were associated with increased mortality at follow up., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: The first-generation ACURATE neo transcatheter heart valve (THV) (Boston Scientific) was associated with a non-negligible occurrence of moderate or greater paravalvular aortic regurgitation (AR) following transcatheter aortic valve replacement. To overcome this issue, the ACURATE neo2 iteration, which incorporates a taller outer skirt aimed at reducing the occurrence of paravalvular AR, has recently been developed., Objectives: The aim of this study was to assess the efficacy and safety of the ACURATE neo2 (Boston Scientific) THV in patients with severe aortic valve stenosis., Methods: ITAL-neo was an observational, retrospective, multicenter registry enrolling consecutive patients with severe aortic valve stenosis, treated with first- and second-generation ACURATE neo THVs, via transfemoral and trans-subclavian access, in 13 Italian centers. One-to-one propensity score matching was applied to account for baseline characteristics unbalance. The primary endpoint was the occurrence of moderate or greater paravalvular AR on predischarge echocardiographic assessment. Secondary endpoints included postprocedural technical success and 90-day device success and safety., Results: Among 900 patients included in the registry, 220 received the ACURATE neo2 THV, whereas 680 were treated with the first-generation device. A total of 410 patients were compared after 1:1 propensity score matching. The ACURATE neo2 THV was associated with a 3-fold lower frequency of postprocedural moderate or greater paravalvular AR (11.2% vs 3.5%; P < 0.001). No other hemodynamic differences were observed. Postprocedural technical success was similar between the 2 cohorts. Fewer adverse events were observed in patients treated with the ACURATE neo2 at 90 days., Conclusions: Transfemoral transcatheter aortic valve replacement using the ACURATE neo2 was associated with a significant lower frequency of moderate or greater paravalvular AR compared with the earlier generation ACURATE neo device, with encouraging short-term safety and efficacy., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: The translation of hemodynamic quantities based on wall shear stress (WSS) or intravascular helical flow into clinical biomarkers of coronary atherosclerotic disease is still hampered by the assumptions/idealizations required by the computational fluid dynamics (CFD) simulations of the coronary hemodynamics. In the resulting budget of uncertainty, inflow boundary conditions (BCs) play a primary role. Accordingly, in this study we investigated the impact of the approach adopted for in vivo coronary artery blood flow rate assessment on personalized CFD simulations where blood flow rate is used as inflow BC., Methods: CFD simulations were carried out on coronary angiograms by applying personalized inflow BCs derived from four different techniques assessing in vivo surrogates of flow rate: continuous thermodilution, intravascular Doppler, frame count-based 3D contrast velocity, and diameter-based scaling law. The impact of inflow BCs on coronary hemodynamics was evaluated in terms of WSS- and helicity-based quantities., Results: As main findings, we report that: (i) coronary flow rate values may differ based on the applied flow derivation technique, as continuous thermodilution provided higher flow rate values than intravascular Doppler and diameter-based scaling law (p = 0.0014 and p = 0.0023, respectively); (ii) such intrasubject differences in flow rate values lead to different surface-averaged values of WSS magnitude and helical blood flow intensity (p<0.0020); (iii) luminal surface areas exposed to low WSS and helical flow topological features showed robustness to the flow rate values., Conclusions: Although the absence of a clinically applicable gold standard approach prevents a general recommendation for one coronary blood flow rate derivation technique, our findings indicate that the inflow BC may impact computational hemodynamic results, suggesting that a standardization would be desirable to provide comparable results among personalized CFD simulations of the coronary hemodynamics., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

The association of left ventricular ejection fraction (LVEF) with procedural and long-term outcomes after state-of-the-art percutaneous coronary intervention (PCI) of bifurcation lesions remains unsettled. A total of 5,333 patients who underwent contemporary coronary bifurcation PCI were included in the intercontinental retrospective combined insights from the unified RAIN (veRy thin stents for patients with left mAIn or bifurcatioN in real life) and COBIS (COronary BIfurcation Stenting) III bifurcation registries. Of 5,003 patients (93.8%) with known baseline LVEF, 244 (4.9%) had LVEF <40% (bifurcation with reduced ejection fraction [BIFrEF] group), 430 (8.6%) had LVEF 40% to 49% (bifurcation with mildly reduced ejection fraction [BIFmEF] group) and 4,329 (86.5%) had ejection fraction (EF) ≥50% (bifurcation with preserved ejection fraction [BIFpEF] group). The primary end point was the Kaplan-Meier estimate of major adverse cardiac events (MACEs) (a composite of all-cause death, myocardial infarction, and target vessel revascularization). Patients with BIFrEF had a more complex clinical profile and coronary anatomy. No difference in procedural (30 days) MACE was observed across EF categories, also after adjustment for in-study outcome predictors (BIFrEF vs BIFmEF: adjusted hazard ratio [adj-HR] 1.39, 95% confidence interval [CI] 0.37 to 5.21, p = 0.626; BIFrEF vs BIFpEF: adj-HR 1.11, 95% CI 0.25 to 2.87, p = 0.883; BIFmEF vs BIFpEF: adj-HR 0.81, 95% CI 0.29 to 2.27, p = 0.683). BIFrEF was independently associated with long-term MACE (median follow-up 21 months, interquartile range 10 to 21 months) than both BIFmEF (adj-HR 2.20, 95% CI 1.41 to 3.41, p <0.001) and BIFpEF (adj-HR 1.91, 95% CI 1.41 to 2.60, p <0.001) groups, although no difference was observed between BIFmEF and BIFpEF groups (adj-HR 0.87, 95% CI 0.61 to 1.24, p = 0.449). In conclusion, in patients who underwent PCI of a coronary bifurcation lesion according to contemporary clinical practice, reduced LVEF (<40%), although a strong predictor of long-term MACEs, does not affect procedural outcomes., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction and Objectives: Coronary artery calcium (CAC) score improves the accuracy of risk stratification for atherosclerotic cardiovascular disease (ASCVD) events compared with traditional cardiovascular risk factors. We evaluated the interaction of coronary atherosclerotic burden as determined by the CAC score with the prognostic benefit of lipid-lowering therapies in the primary prevention setting., Methods: We reviewed the MEDLINE, EMBASE, and Cochrane databases for studies including individuals without a previous ASCVD event who underwent CAC score assessment and for whom lipid-lowering therapy status stratified by CAC values was available. The primary outcome was ASCVD. The pooled effect of lipid-lowering therapy on outcomes stratified by CAC groups (0, 1-100,> 100) was evaluated using a random effects model., Results: Five studies (1 randomized, 2 prospective cohort, 2 retrospective) were included encompassing 35 640 individuals (female 38.1%) with a median age of 62.2 [range, 49.6-68.9] years, low-density lipoprotein cholesterol level of 128 (114-146) mg/dL, and follow-up of 4.3 (2.3-11.1) years. ASCVD occurrence increased steadily across growing CAC strata, both in patients with and without lipid-lowering therapy. Comparing patients with (34.9%) and without (65.1%) treatment exposure, lipid-lowering therapy was associated with reduced occurrence of ASCVD in patients with CAC> 100 (OR, 0.70; 95%CI, 0.53-0.92), but not in patients with CAC 1-100 or CAC 0. Results were consistent when only adjusted data were pooled., Conclusions: Among individuals without a previous ASCVD, a CAC score> 100 identifies individuals most likely to benefit from lipid-lowering therapy, while undetectable CAC suggests no treatment benefit., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose: To investigate the impact of pulmonary artery catheter (PAC) monitoring on survival of cardiogenic shock(CS), in the light of the controversies in available evidence., Materials and Methods: MEDLINE, EMBASE, Cochrane library and Web of Science were systematically screened to identify most relevant studies on patients with CS comparing PAC use to non-use during hospital stay. Short-term mortality was the primary endpoint and the use of Mechanical Circulatory Support (MCS) devices was the secondary one., Results: Six observational studies including 1,166,762 patients were selected. The most frequent etiology of CS was post-myocardial infarction (75% [95% CI 55-89%] in PAC-group and 81%[95% CI 47-95%] in non-PAC group). Overall, PAC was used in 33%(95% CI 24-44%) of cases. Pooling data adjusted for confounders, a significant association between the PAC-group and a reduction in short-term mortality emerged when compared to the non-PAC group (36%[95% CI 27-45%] vs 47%[95% CI 35-59%];AdjustedOR 0.71, 95% CI 0.59-0.87, p < 0.01). MCS use was significantly higher in PAC vs non-PAC group (59% [95% CI 54-65%]) vs 48% [95% CI 43-53%]);OR 1.60 [95% CI 1.27-2.02, p < 0.01])., Conclusions: PAC was associated with lower incidence of short-term mortality in CS pooling adjusted observational studies. Prospective studies are needed to confirm our hypothesis and better clarify the mechanisms of this potential prognostic benefit., Competing Interests: Declaration of Competing Interest None declared., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Change in longitudinal left ventricular (LV) systolic function serves as an early marker of the deleterious effect of aortic stenosis (AS) and other cardiac comorbidities on cardiac function. We explored the prognostic value of tissue Doppler imaging (TDI)-derived longitudinal LV systolic function, defined by the peak systolic average of lateral and septal mitral annular velocities (average S') among symptomatic patients with severe AS undergoing transcatheter aortic valve implantation (TAVI). 297 consecutive patients with severe AS undergoing TAVI at three european centers with available average S' at preprocedural echocardiography were retrospectively included. The primary endpoint was the Kaplan Meier estimate of all-cause mortality. After a median 18 months (IQR 12-18) follow-up, 36 (12.1%) patients had died. Average S' was associated with all-cause mortality (per 1 cm/sec decrease: HR 1.29, 95%CI 1.03-1.60, p = 0.025), the cut-off of 6.5 cm/sec being the most accurate. Patients with average S' < 6.5 cm/sec (55.2%) presented characteristics of more advanced LV remodeling and functional impairment along with higher burden of cardiac comorbidities, and experienced higher all-cause mortality (17.6% vs. 7.5%, p = 0.007), also when adjusted for in-study outcome predictors (adj-HR: 2.69, 95%CI 1.22-5.93, p = 0.014). Results were consistent among patients with preserved ejection fraction, normal-flow AS, high-gradient AS and in those without LV hypertrophy. Longitudinal LV systolic function assessed by average S' is independently associated with long-term all-cause mortality among TAVI patients. An average S' below 6.5 cm/sec best defines clinically meaningful reduced longitudinal systolic function and may aid clinical risk stratification in these patients., (© 2022. The Author(s).)

Background: The adoption of Computed tomography (CT)-defined sarcopenia to risk stratify transcatheter aortic valve implantation (TAVI) candidates remains limited by a lack of both standardized definition and evidence of independent value over currently adopted mortality prediction tools., Methods: 391 consecutive TAVI patients with pre-procedural CT scan were included (81 ​± ​6 years, 57.5% male, STS-PROM score 4.4 ​± ​3.6%) and abdominal muscle retrospectively quantified. The two definitions of radiologic sarcopenia previously adopted in TAVI studies were compared (psoas muscle area [PMA] at the L4 vertebra level: "PMA-sarcopenia"; indexed skeletal muscle area at the L3 vertebra level: "SMI-sarcopenia"). The primary endpoint was longer available-term all-cause mortality. Secondary endpoints were Valve Academic Research Consortium-2-defined in-hospital and 30-day outcomes., Results: SMI- and PMA-sarcopenia were present in 192 (49.1%) and 117 (29.9%) patients, respectively. After a median of 24 (12-30) months follow-up, 83 (21.2%) patients died. PMA-(adj-HR 1.81, 95%CI 1.12-2.93, p ​= ​0.015), but not SMI-sarcopenia (adj-HR 1.23, 95%CI 0.76-2.00, p ​= ​0.391), was associated with all-cause mortality independently of age, sex and in-study outcome predictors (atrial fibrillation, hemoglobin, history of peripheral artery disease, cancer and subcutaneous adipose tissue). PMA-defined sarcopenia provided additive prognostic value over current post-TAVI mortality risk estimators including STS-PROM (p ​= ​0.001), Euroscore II (p ​= ​0.025), Charlson index (p ​= ​0.025) and TAVI2-score (p ​= ​0.020). Device success, early safety, clinical efficacy and 30-day all-cause death were unaffected by sarcopenia status regardless of definition., Conclusions: PMA-sarcopenia (but not SMI-sarcopenia) is predictive of 2 year mortality among TAVI patients. The prognostic information provided by PMA-sarcopenia is independent of the tools currently adopted to predict post-TAVI mortality in clinical practice., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2021 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Data regarding management of patients with unprotected left main coronary artery in-stent restenosis (LM-ISR) are scarce., Objectives: This study investigated the safety and effectiveness of percutaneous coronary intervention (PCI) vs. coronary artery bypass grafting (CABG) for the treatment of unprotected LM-ISR., Methods: Consecutive patients who underwent PCI or CABG for unprotected LM-ISR were enrolled. The primary endpoint was a composite of major adverse cardiac and cerebrovascular events (MACCE), defined as cardiac death, myocardial infarction (MI), target vessel revascularization (TVR), and stroke., Results: A total of 305 patients were enrolled, of which 203(66.6%) underwent PCI and 102(33.4%) underwent CABG. At 30-day follow-up, a lower risk of cardiac death was observed in the PCI group, compared with the CABG-treated group (2.1% vs. 7.1%, HR 3.48, 95% CI 1.01-11.8, p = 0.04). At a median of 3.5 years [interquartile range ( IQR ) 1.3-5.5] follow-up, MACCE occurred in 27.7% vs. 29.6% ( HR 0.82, 95% CI 0.52-1.32, p = 0.43) in PCI- and CABG-treated patients, respectively. There were no significant differences between PCI and CABG in cardiac death (9.9% vs. 18.4%; HR 1.56, 95% CI 0.81-3.00, p = 0.18), MI (7.9% vs. 5.1%, HR 0.44, 95% CI 0.15-1.27, p = 0.13), or stroke (2.1% vs. 4.1%, HR 1.79, 95% CI 0.45-7.16, p = 0.41). TVR was more frequently needed in the PCI group (15.2% vs. 6.1%, HR 0.35, 95% CI 0.15-0.85, p = 0.02)., Conclusions: This analysis of patients with LM-ISR revealed a lower incidence of cardiac death in PCI compared with CABG in short-term follow-up. During the long-term follow-up, no differences in MACCE were observed, but patients treated with CABG less often required TVR., Visual Overview: A visual overview is available for this article., Registration: https://www.clinicaltrials.gov; Unique identifier: NCT04968977., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wańha, Bil, Kołodziejczak, Kowalówka, Kowalewski, Hudziak, Gocoł, Januszek, Figatowski, Milewski, Tomasiewicz, Kübler, Hrymniak, Desperak, Kuźma, Milewski, Góra, Łoś, Kulczycki, Włodarczak, Skorupski, Grygier, Lesiak, D'Ascenzo, Andres, Kleczynski, Litwinowicz, Borin, Smolka, Reczuch, Gruchała, Gil, Jaguszewski, Bartuś, Suwalski, Dobrzycki, Dudek, Bartuś, Ga̧sior, Ochała, Lansky, Deja, Legutko, Kedhi and Wojakowski.)

Cardiogenic shock represents one of the most dramatic scenarios to deal with in intensive cardiology care and is burdened by substantial short-term mortality. An integrated approach, including timely diagnosis and phenotyping, along with a well-established shock team and management protocol, may improve survival. The use of the Swan-Ganz catheter could play a pivotal role in various phases of cardiogenic shock management, encompassing diagnosis and haemodynamic characterisation to treatment selection, titration and weaning. Moreover, it is essential in the evaluation of patients who might be candidates for long-term heart-replacement strategies. This review provides a historical background on the use of the Swan-Ganz catheter in the intensive care unit and an analysis of the available evidence in terms of potential prognostic implications in this setting., Competing Interests: Disclosure: The authors have no conflicts of interest to declare., (Copyright © 2022, Radcliffe Cardiology.)

We performed an updated meta-analysis to robustly quantify admission trends of patients with ST-segment elevation MI (STEMI) and non-ST-segment elevation MI (NSTEMI) during the first wave of the pandemic and to characterize on a large basis the risk profile and early prognosis. Studies having the same observation period for the comparison between SARS-CoV-2 outbreak in 2020 versus control period in 2019 were included. Primary endpoints were the relative variation of hospital admissions, the difference of in-hospital mortality for STEMI and NSTEMI. Secondary were: mortality according to countries, income levels and data quality; cardiogenic shock, mechanical complications, door-to-balloon time, time from symptom onset to first medical contact, left ventricular ejection fraction (LVEF) and troponin. In total, 61 observational studies with 125,346 patients were included. Compared with 2019, during the pandemic for STEMI were observed: a 24% reduction of hospitalizations with an impact on early survival (OR = 1.33 in-hospital mortality); the time from symptom onset to first medical contact was 91.31 min longer, whereas door-to-balloon time was increased (+5.44 min); after STEMI, the rate of cardiogenic shock was 33% higher; LVEF at discharge was decreased (-3.46); elevated high-sensitivity troponin levels (1.52) on admission. For NSTEMI, in the COVID-19 period, we observed a 31% reduction of hospitalizations and higher in-hospital deaths (OR = 1.34). The highest mortality rates among countries were: Italy OR = 3.71 (high income), Serbia OR = 2.15 (upper middle) and Pakistan OR = 1.69 (lower middle). Later hospital presentation was associated with larger infarctions, as well as with increased cardiogenic shock and in-hospital mortality.

Background: The safety and efficacy of potent P2Y12 inhibitors (Ticagrelor and Prasugrel) in dual antiplatelet therapy (DAPT) with aspirin in elderly acute coronary syndrome (ACS) patients remains unclear., Methods: All ACS patients aged 75 years and older treated with Percutaneous Coronary Intervention (PCI) from PRAISE dataset were included. The safety and efficacy of Ticagrelor vs Clopidogrel was evaluated with inverse probability of treatment weighting (IPTW). Sensitivity analysis was performed for patients older or equal than 85 years old. All-cause mortality was the primary endpoint, while myocardial infarction (MI), Bleeding Academic Research Consortium (BARC) 3-5 bleedings and Major and Net Adverse Clinical and Cardiac Events (MACE and NACE) were the secondary ones., Results: 4287 patients were included, 3197 treated with Clopidogrel and 1090 with Ticagrelor. After 16 ± 3 months, Ticagrelor showed neutral effect on NACE and mortality (HR 0.98; 0.63-1.52, p = 0.94 and HR 0.38; 0.14-1.04, p = 0,06), reduced risk of MACE and MI (HR 0.82; 0.23-0.91, p = 0.03 and HR 0.43; 0.14-0.89, p = 0.04) and increased risk of BARC 3-5 bleeding (HR 2.14; 1.19-3.85, p = 0.001). In very elderly patients (≥85 years) Ticagrelor decreased risk of MI and increased risk of bleeding (HR 0.69; 0.22-0.95, p = 0.04 and HR 2.36; 1.02-5.52, p = 0.04, all 95%CI) with neutral effect on NACE and MACE., Conclusions: In elderly ACS patients treated with PCI, Ticagrelor was associated with neutral effect on all-cause mortality, lower risk MACE and MI compared with Clopidogrel. Such benefit was counterbalanced by increased risk of major bleedings. These results were consistent among patients aged 85 years and older., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has rapidly spread globally. Due to different testing strategies, under-detection of positive subjects and COVID-19-related-deaths remains common. Aim of this analysis was to assess the real impact of COVID-19 through the analysis of 2020 Italian all-cause mortality data compared to historical series., Methods: We performed a retrospective analysis of 2020 and 2015-2019 all-cause mortality data released by the Italian National Institute for Statistics (ISTAT) for the time period January 1 st -March 21 st . This preliminary sample included 1084 Italian municipalities showing at least 10 deaths during the above-mentioned timeframe and an increase in mortality of more than 20% as compared to the previous five years (2015-2019), with a resulting coverage of 21% of Italian population. The difference between 2020 observed and expected deaths (mean of weekly deaths in 2015-2019) was computed, together with mortality rate ratio (MRR) for each of the four weeks following detection of the first autochthonous COVID-19 case in Italy (February 23 rd , 2020 - March 21 st , 2020), as well as for this entire timeframe. Subgroup analysis by age groups was also performed., Results: Overall MRR was 1.79 [1.75-1.84], with an observed excess mortality of 8750 individuals in the investigated sample, which in itself outweighs Italian Civil Protection report of only 4,825 COVID-19-related deaths across Italy, as of March 21. Subgroup analysis did not show any difference in mortality rate in '0-14 years' age group, while MRRs were significantly increased in older age groups, in particular in patients >75 years (MRR 1.84 [1.79-1.89]). In addition, week-by-week analysis showed a progressive increase in MRR during this period, peaking in the last week (March 15 th , 2020 - March 21 st , 2020) with an estimated value of 2.65 [2.53-2.78]., Conclusions: The analysis of all-cause mortality data in Italy indicates that reported COVID-19-related deaths are an underestimate of the actual death toll. All-cause death should be seen as the epidemiological indicator of choice to assess the real mortality impact exerted by SARS-CoV-2, given that it also best reflects the toll on frail patient subsets (e.g. the elderly or those with cardiovascular disease).

Background: Whereas the efficacy and safety of intravascular lithotripsy (IVL) have been confirmed in de novo calcified coronary lesions, little is known about its utility in treating stent underexpansion. This study aimed to investigate the impact of IVL in treating stent underexpansion. Methods and Results: Consecutive patients with stent underexpansion treated with IVL entered the multicenter IVL-Dragon Registry. The procedural success (primary efficacy endpoint) was defined as a relative stent expansion >80%. Thirty days device-oriented composite endpoint (DOCE) (defined as a composite of cardiac death, target lesion revascularization, or target vessel myocardial infarction) was the secondary endpoint. A total of 62 patients were enrolled. The primary efficacy endpoint was achieved in 72.6% of patients. Both stent underexpansion 58.5% (47.5−69.7) vs. 11.4% (5.8−20.7), p < 0.001, and the stenotic area 82.6% (72.4−90.8) vs. 21.5% (11.1−37.2), p < 0.001, measured by quantitative coronary angiography improved significantly after IVL. Intravascular imaging confirmed increased stent expansion following IVL from 37.5% (16.0−66.0) to 86.0% (69.2−90.7), p < 0.001, by optical coherence tomography and from 57.0% (31.5−77.2) to 89.0% (85.0−92.0), p = 0.002, by intravascular ultrasound. Secondary endpoint occurred in one (1.6%) patient caused by cardiac death. There was no target lesion revascularization or target vessel myocardial infarction during the 30-day follow-up. Conclusions: In this real-life, largest-to-date analysis of IVL use to manage underexpanded stent, IVL proved to be an effective and safe method for facilitating stent expansion and increasing luminal gain.

Antecedent use of renin-angiotensin system inhibitors (RASi) prevents clinical deterioration and protects against cardiovascular/thrombotic complications of COVID-19, for indicated patients. Uncertainty exists regarding treatment continuation throughout infection and doing so with concomitant medications. Hence, the purpose of this study is to evaluate the differential effect of RASi continuation in patients hospitalized with COVID-19 according to diuretic use. We used the Coracle registry, which contains data of hospitalized patients with COVID-19 from 4 regions of Italy. We used Firth logistic regression for adult (>50 years) cases with admission on/after February 22, 2020, with a known discharge status as of April 1, 2020. There were 286 patients in this analysis; 100 patients (35.0%) continued RASi and 186 (65%) discontinued. There were 98 patients treated with a diuretic; 51 (52%) of those continued RASi. The in-hospital mortality rates in patients treated with a diuretic and continued versus discontinued RASi were 8% versus 26% (p = 0.0179). There were 188 patients not treated with a diuretic; 49 (26%) of those continued RASi. The in-hospital mortality rates in patients not treated with a diuretic and continued versus discontinued RASi were 16% versus 9% (p = 0.1827). After accounting for age, cardiovascular disease, and laboratory values, continuing RASi decreased the risk of mortality by approximately 77% (odds ratio 0.23, 95% confidence interval 0.06 to 0.95, p = 0.0419) for patients treated with diuretics, but did not alter the risk in patients treated with RASi alone. Continuing RASi in patients concomitantly treated with diuretics was associated with reduced in-hospital mortality., Competing Interests: Disclosures The authors have no conflicts of interest to declare., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Aims: The revascularization strategy to pursue in older myocardial infarction (MI) patients with multivessel disease (MVD) is currently unknown. For this reason, while waiting for the results of dedicated trials, we sought to compare a complete versus a culprit-only strategy in older MI patients by merging data from four registries., Methods and Results: The inclusion criteria for the target population of the present study were (i) age ≥ 75 years; (ii) MI (STE or NSTE); (iii) MVD; (iv) successful treatment of culprit lesion. Propensity scores (PS) were derived using logistic regression (backward stepwise selection, p < 0.2). The primary outcome was all-cause mortality. Secondary outcomes were cardiovascular (CV) death, MI, and major bleeding. Multivariable adjustment included the PS and inverse probability of treatment weighting (IPTW). The Kaplan-Meier plots were weighted for IPT. Among 2087 patients included, 1362 (65%) received culprit-only treatment whereas 725 (35%) complete revascularization. The mean age was 81.5 years, while the mean follow-up was 419 ± 284 days. Seventy-four patients (10%) died in the complete group and 223 in the culprit-only one (16%). The adjusted cumulative 1-year mortality was 9.7% in the complete and 12.9% in the culprit-only group (adjusted HR: 0.67, 95% CI: 0.50-0.89). Complete revascularization was associated with lower incidence of CV death (adjusted HR: 0.68, 95% CI: 0.48-0.95) and MI (adjusted HR 0.67, 95% CI: 0.48-0.95)., Conclusions: Culprit-only is the default strategy in older MI patients with MVD. In our analysis, complete revascularization was associated with lower all-cause and CV mortality and with a lower MI rate., (© 2022 Wiley Periodicals LLC.)

Introduction: Data regarding the duration of dual antiplatelet therapy (DAPT) in patients with drug-eluting stent restenosis (DES-ISR) treated with percutaneous coronary intervention (PCI) and drug-eluting balloons (DEB) or DES are not unambiguous., Aim: To evaluate the relationship between long-term outcomes and the length of DAPT in patients treated with PCI due to DES-ISR with DEB or DES., Material and Methods: Overall, a total of 1,367 consecutive patients with DES-ISR, who underwent PCI with DEB or DES between 2008 and 2019 entered the study. The mean length of the follow-up was 1,298.7 ±794 days. We assessed study endpoints according to the duration of DAPT (≤ 3 vs. > 3 and ≤ 6 vs. > 6 months) before and after propensity score matching (PSM): stroke, target lesion revascularisation (TLR), target vessel revascularisation (TVR), myocardial infarction (MI), death and device oriented composite endpoints (DOCE). Kaplan-Meier estimates were created to differentiate long-term outcomes., Results: Pairwise contrast analysis considering type of PCI (DES vs. DEB) and duration of DAPT (≤ 6 vs. > 6 months) before PSM revealed superiority of DES + DAPT > 6 months vs. DEB + DAPT > 6 months for DOCE ( p < 0.001), TVR ( p = 0.02) and TLR ( p = 0.01). Also, DES + DAPT ≤ 6 months was found to be superior compared to DEB + DAPT ≤ 6 months for DOCE ( p < 0.001), TVR ( p = 0.02) and TLR ( p = 0.01). Kaplan-Meier estimate analysis confirmed that DAPT > 6 months is related to a higher stroke rate ( p = 0.01) when compared to ≤ 6 months., Conclusions: Treatment with DAPT in patients with DES-ISR is related to better long-term outcomes in the case of PCI with DES than DEB. DAPT > 6 months is related to the greater rate of strokes, independently of the type of treatment (DES and DEB) than DAPT ≤ 6 months., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 Termedia Sp. z o. o.)

Background Controversy exists over whether sex has significant interaction with revascularization strategy for unprotected left main coronary artery disease. Higher mortality has been reported among women treated with percutaneous coronary intervention compared with coronary artery bypass grafting. Methods and Results The DELTA (Drug-Eluting Stents for Left Main Coronary Artery Disease) and DELTA-2 registries are international, multicentric registries evaluating the outcomes of subjects undergoing coronary revascularization for unprotected left main coronary artery disease. The primary outcome was a composite of death, myocardial infarction, or cerebrovascular accidents. The population consisted of 6253 patients, including 1689 (27%) women. Women were older and more likely to have diabetes and chronic kidney disease than men ( P <0.05). At a median follow-up of 29 months (interquartile range 12-49), a significant interaction between sex and revascularization strategy was observed for the primary end point (p int =0.012) and all-cause death (p int =0.037). Among women, compared with percutaneous coronary intervention, coronary artery bypass grafting was associated with lower risk of the primary end point (event rate 9.5% versus 15.3%; adjusted hazard ratio [AHR], 0.53; 95% CI, 0.35-0.79, P <0.001) and all-cause death (event rate 5.6% versus 11.7% AHR, 0.50; 95% CI, 0.30-0.82) and no significant differences were observed in men. Conclusions In women undergoing coronary revascularization for unprotected left main coronary artery disease, coronary artery bypass grafting was associated with lower risk of death, myocardial infarction, or cerebrovascular accidents whereas no significant differences between coronary artery bypass grafting and percutaneous coronary intervention were observed in men. Further dedicated studies are needed to determine the optimal revascularization strategy in women with unprotected left main coronary artery disease.

Background: Patient-related and lesion-related factors may influence instantaneous wave-free ratio (iFR)/fractional flow reserve (FFR) concordance, potentially affecting the safety of revascularization deferral., Methods: Consecutive patients with at least an intermediate coronary stenosis evaluated by both iFR and FFR were retrospectively enrolled. The agreement between iFR and FFR at their diagnostic cut-offs (FFR 0.80, iFR 0.89) was assessed. Predictors of discordance were assessed using multivariate analyses. Tailored iFR cut-offs according to predictors of discordance best matching an FFR of 0.80 were identified. The impact of reclassification according to tailored iFR cut-offs on major cardiovascular events (MACE: cardiovascular death, myocardial infarction or target-lesion revascularization) among deferred lesions was investigated., Results: Two hundred and ninety-nine intermediate coronary stenosis [FFR 0.84 (0.78-0.89), iFR 0.91 (0.87-0.95), 202 left main/left anterior descending (LM/LAD) vessels, 67.6%] of 260 patients were studied. Discordance rate was 23.4% (n = 70, 10.7% iFR-negative discordant, 12.7% iFR-positive discordant). Predictors of discordance were LM/LAD disease, multivessel disease, non-ST-elevation myocardial infarction, smoking, reduced eGFR and hypertension. Lesion reclassification with tailored iFR cut-offs based on patient-level predictors carried no prognostic value among deferred lesions. Reclassification according to lesion location, which was entirely driven by LM/LAD lesions (iFR cut-offs: 0.93 for LM/LAD, 0.89 for non-LM/LAD), identified increased MACE among lesions deferred based on a negative FFR, between patients with a positive as compared with a negative iFR (19.4 vs. 6.1%, P = 0.044), whereas the same association was not observed with the conventional 0.89 iFR cut-off (15 vs. 8.6%, P = 0.303)., Conclusion: Tailored vessel-based iFR cut-offs carry prognostic value among FFR-negative lesions, suggesting that a one-size-fit-all iFR cut-off might be clinically unsatisfactory., (Copyright © 2021 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Ethnic disparities have been reported in cardiovascular disease. However, ethnic disparities in takotsubo syndrome (TTS) remain elusive. This study assessed differences in clinical characteristics between Japanese and European TTS patients and determined the impact of ethnicity on in-hospital outcomes., Methods: TTS patients in Japan were enrolled from 10 hospitals and TTS patients in Europe were enrolled from 32 hospitals participating in the International Takotsubo Registry. Clinical characteristics and in-hospital outcomes were compared between Japanese and European patients., Results: A total of 503 Japanese and 1670 European patients were included. Japanese patients were older (72.6 ± 11.4 years vs. 68.0 ± 12.0 years; p < 0.001) and more likely to be male (18.5 vs. 8.4%; p < 0.001) than European TTS patients. Physical triggering factors were more common (45.5 vs. 32.0%; p < 0.001), and emotional triggers less common (17.5 vs. 31.5%; p < 0.001), in Japanese patients than in European patients. Japanese patients were more likely to experience cardiogenic shock during the acute phase (15.5 vs. 9.0%; p < 0.001) and had a higher in-hospital mortality (8.2 vs. 3.2%; p < 0.001). However, ethnicity itself did not appear to have an impact on in-hospital mortality. Machine learning approach revealed that the presence of physical stressors was the most important prognostic factor in both Japanese and European TTS patients., Conclusion: Differences in clinical characteristics and in-hospital outcomes between Japanese and European TTS patients exist. Ethnicity does not impact the outcome in TTS patients. The worse in-hospital outcome in Japanese patients, is mainly driven by the higher prevalence of physical triggers., Trial Registration: URL: https://www.clinicaltrials.gov ; Unique Identifier: NCT01947621., (© 2021. The Author(s).)

Objectives: to test the safety and efficacy of intravascular imaging and specifically optical coherence tomography (OCT) as a diagnostic tool for left main angioplasty and analyze the mid-term outcome accordingly., Background: Clinical data and international guidelines recommend the use of intravascular imaging ultrasound (IVUS) to guide left main (LM) angioplasty. Despite early experience using OCT in this setting is encouraging, the evidence supporting its use is still limited., Methods: ROCK II is a multicenter, investigator-driven, retrospective European study to compare the performance of IVUS and OCT versus angiography in patients undergoing distal-LM stenting. The primary study endpoint was target-lesion failure (TLF) including cardiac death, target-vessel myocardial infarction and target-lesion revascularization. We designed this study hypothesizing the superiority of intravascular imaging over angiographic guidance alone, and the non-inferiority of OCT versus IVUS., Results: A total of 730 patients, 377 with intravascular-imaging guidance (162 OCT, 215 IVUS) and 353 with angiographic guidance, were analyzed. The one-year rate of TLF was 21.2% with angiography and 12.7% with intravascular-imaging (p = 0.039), with no difference between OCT and IVUS (p = 0.26). Intravascular-imaging was predictor of freedom from TLF (HR 0.46; 95% CI 0.23-0.93: p = 0.03). Propensity-score matching identified three groups of 100 patients each with no significant differences in baseline characteristics. The one-year rate of TLF was 16% in the angiographic, 7% in the OCT and 6% in the IVUS group, respectively (p = 0.03 for IVUS or OCT vs. angiography). No between-group significant differences in the rate of individual components of TLF were found., Conclusions: Intravascular imaging was superior to angiography for distal LM stenting, with no difference between OCT and IVUS., (© 2021 Wiley Periodicals LLC.)

Objectives: We aimed to compare the incidence and timing of major adverse cardiovascular events (MACE) within the first year after spontaneous coronary artery dissection (SCAD) according to the management strategy: conservative versus invasive., Background: Treatment of SCAD remains controversial., Methods: A pooled analysis of studies providing separate individual clinical outcomes for conservative and invasive treatment strategies within 1 year after SCAD was performed. The primary outcome measure was MACE incidence within three predefined study periods after SCAD, namely "in-hospital", "discharge-to-6-months" and "6-to-12-months". MACE was defined as a composite of all-cause death, myocardial infarction, target vessel revascularization, heart failure and SCAD recurrence., Results: A total of 16 studies (444 patients) were included; 277 (62%) patients were treated conservatively and 167 (38%) invasively. Within 1-year follow-up, 39 (67%) MACE occurred during the in-hospital period compared to 10 (17%) in the "discharge-to-6 months" period and 9 (16%) in the "6-to-12-months" period (p < 0.0001 for the overall comparison). MACE incidence was also significantly different between the three study periods in the conservatively-treated group (23 [78%] vs. 7 [23%] vs. 0 [0%], respectively; p < 0.0001) and the invasively-treated group (12 [66%] vs. 3 [17%] vs. 3 [17%], respectively; p < 0.0001), although no significant difference was found regarding MACE incidence in the intra-period comparisons between conservative and invasive treatment strategies., Conclusions: This pooled analysis showed that most MACE following SCAD occurred during the in-hospital period compared to the following two semesters, regardless of the treatment strategy. No difference regarding MACE incidence was found between conservative and invasive strategies in each study period., (© 2021 Wiley Periodicals LLC.)

Background: A polymer-free biolimus-eluting stent (PF-BES) and a zotarolimus-eluting stent (ZES) recently showed similar clinical profiles and appear to be competing options in specific clinical settings of patients undergoing percutaneous coronary intervention (PCI). Whether they perform similarly also in complex procedural settings as coronary bifurcation lesions remains unaddressed., Methods: All consecutive patients undergoing coronary bifurcation PCI with PF-BES or the new iteration of the ZES from three large multicenter real-world registries were included. The primary outcome was major adverse cardiovascular events (MACE), a composite of all-cause death, myocardial infarction (MI), target lesion revascularization (TLR) and stent thrombosis (ST). Multiple analyses to adjust for baseline differences were carried out including propensity-score matching, propensity-score stratification and inverse-probability-weighting. Outcomes are reported according to Cox proportional hazard models censored at 400-day follow-up., Results: 1169 patients treated with PF-BES (n = 440) or ZES (n = 729) on the main branch of a coronary bifurcation lesion were included (mean age 69 ± 11 years, 75.4% male, 53.8% acute coronary syndrome at presentation, 26.6% left main bifurcation, median dual antiplatelet therapy duration 12 [range 12-12] months). MACE, all-cause death, TLR and ST tended towards non-statistically higher rates with the PF-BES as compared to the ZES. Higher MI and target vessel revascularization occurrence was observed with PF-BES., Conclusions: In this large contemporary cohort of patients undergoing coronary bifurcation PCI, the occurrence of MACE was non-statistically different with the use of PF-BES and ZES devices. However, differences favoring the ZES device that may entail clinical relevance were observed. Further studies are needed to confirm these findings and explore whether they remain valid when a short dual antiplatelet therapy is adopted., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Artificial intelligence (AI) comprises a wide range of technologies and methods with heterogeneous degrees of complexity, applications, and abilities. In the cardiovascular field, AI holds the potential to fulfil many unsolved challenges, eventually translating into improved patient care. In particular, AI appears as the most promising tool to overcome the gap between ever-increasing data-rich technologies and their practical implementation in cardiovascular research, in the cardiologist routine, in the patient daily life and at the healthcare-policy level. A multiplicity of AI technologies is progressively pervading several aspects of precision cardiovascular medicine including early diagnosis, automated imaging processing and interpretation, disease sub-phenotyping, risk prediction and remote monitoring systems. Several methodological, logistical, educational, and ethical challenges are emerging by integrating AI systems at any stage of cardiovascular medicine. This review will discuss the basics of AI methods, the growing body of evidence supporting the role of AI in the cardiovascular field and the challenges to overcome for an effective AI-integrated cardiovascular medicine.

Aims: To evaluate the impact of systematic predilation with balloon aortic valvuloplasty (BAV) on transcatheter aortic valve implantation (TAVI)., Methods and Results: We performed a systematic meta-analysis investigating patients undergoing TAVI with systematic BAV vs no BAV in RCT or in adjusted studies. Device success was the primary endpoint, while all-cause mortality, 30-day moderate/severe aortic regurgitation (AR), stroke, permanent pacemaker implantation (PPI) and acute kidney injury (AKI) were the secondary endpoints. Subanalysis according to design of the study (RCT and adjusted analysis) and to the type of valve (balloon-expandable [BE] vs self-expanding [SE]) were conducted. We obtained data from 15 studies, comprising 16,408 patients: 10,364 undergoing BAV prior to TAVI and 6,044 in which direct TAVI has been performed. At 30-day follow-up, BAV did not improve the rate of device success in the overall population (OR, 1.09; 95% CI, 0.90-1.31), both in SE (OR, 0.93; 95% CI, 0.60-1.45) and in BE (OR, 1.16; 95% CI, 0.88-1.52) valves. Between BAV and direct TAVI, no differences in secondary outcomes were observed neither in overall population nor according to valve type between BAV and direct TAVI strategies. All endpoints results were consistent between RCTs and adjusted studies except for postdilation rate that did not differ in observational studies (OR, 0.70; 95% CI, 0.47-1.04), while it was lower in BAV when only RCTs were included in the analysis (OR, 0.48; 95% CI, 0.24-0.97)., Conclusions: Direct TAVI is feasible and safe compared to predilation approach with similar device success rates and clinical outcomes. Direct TAVI could represent a first-choice approach in contemporary TAVI procedures.

Aims: Dual antiplatelet therapy (DAPT) with a P2Y12 inhibitor on top of aspirin is the cornerstone of therapy after acute coronary syndromes (ACS). Nonetheless, the safest and most efficacious P2Y12 for older patients who are both at high ischaemic and bleeding risk remains uncertain. We aimed to examine the effect of available P2Y12 inhibitors on ischaemic and bleeding endpoints in older adults with ACS., Methods and Results: Randomized clinical trials that reported separately the results of adults older >70 years for at least the primary endpoint [composite of death, myocardial infarction (MI), and stroke]. Seven studies (14 485 patients-years) were included. Network meta-analysis showed that prasugrel was associated with similar occurrence of the primary endpoint and of a secondary ischaemic endpoint (composite of MI and stroke) and was most likely the best treatment [Surface Under the Cumulative Ranking curve Analysis (SUCRA) 54.5 and 59.8, respectively]. With regards to major bleedings, clopidogrel showed the highest likelihood of event reduction (SUCRA 70.1%), while ticagrelor of stent thrombosis (SUCRA 55.6%). Our meta-regression with a fixed proportion of patients managed invasively of 100% confirmed these trends with increasing SUCRA., Conclusion: Among older subjects with ACS, DAPT should be balanced upon ischaemic and bleeding risks as prasugrel is associated with the highest probability of reduction of ischaemic events and clopidogrel of bleedings. Ticagrelor had highest SUCRA for stent thrombosis reduction but seems suboptimal in older adults., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: The placebo effect is a well described phenomenon in blinded studies evaluating antianginal therapeutics, although its effect on clinical research metrics remains unknown. We conducted a systematic review and meta-analysis to quantify the effect of placebo on end points of symptoms, life quality, and functional outcomes in randomized placebo-controlled trials (RCTs) of symptomatic stable coronary artery disease., Methods: We systematically reviewed MEDLINE, EMBASE, and the Cochrane database for double-blind RCTs of antiangina therapeutics. Patients randomized to the placebo arm were the study population. Main outcomes were the changes in exercise performance (exercise treadmill test [ETT] parameters), quality of life (Seattle Angina Questionnaire domains), symptoms (Canadian Cardiovascular Society angina class) and drug usage (nitroglycerin tablets per week) between baseline and after placebo treatment. The primary outcome was ETT total duration time. Data were pooled with a random effect model., Results: Seventy-eight RCTs (83% drug-controlled, 17% procedure-controlled) were included encompassing 4925 patients randomized to placebo. ETT total duration time was significantly improved after placebo treatment compared with baseline (mean, 29.2; 95% confidence interval, 20.6-37.8] seconds) with evidence of high heterogeneity (I 2  = 98%) At subgroup analysis, crossover design was associated with a smaller placebo effect on ETT performance than parallel study design (P for interaction = 0.001). A significant placebo effect was observed for all secondary outcomes with overall high heterogeneity., Conclusions: A substantial placebo effect was present in angina RCTs across a variety of functional and life quality metrics. High variability in placebo effect size was present, mostly unexplained by differences in study and patient characteristics., (Copyright © 2021 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)